Mammalian ornithine decarboxylase (ODC) is subject to a form of feedback regulation whereby polyamines, the product of the metabolic pathway initiated by ODC, cause a prompt reduction of enzymatic activity when their level becomes high within cells. This process occurs post- translationally, but its mechanism is not well understood. ODC of the parasite Trypanosome brucei is structurally similar to mammalian ODC, but is not regulated in this way. Utilizing cloned genes from the parasite and from mouse, we will employ reverse-genetic and biochemical approaches to studying this problem. In addition, transgenic mice will be used to determine whether the regulatory process mediates significant biological functions in the intact organism.